New Understanding of Chronic Pain

New Understanding of Chronic Pain

In their new study, the scientists found that DMS, a small-molecule by-product of cellular membranes in the nervous system, is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected. The findings suggest inhibiting this molecule may be a fruitful target for drug development.

"We think that this is a big step forward in understanding and treating neuropathic pain, and also a solid demonstration of the power of metabolomics," said Doctor Gary J. Patti of Washington University in St. Louis.

Scientists who want to understand what makes diseased cells different from healthy cells have often looked for differences in levels of gene expression or cellular proteins — approaches known respectively as genomics and proteomics. Metabolomics, by contrast, concerns differences in the levels of small-molecule metabolites, such as sugars, vitamins, and amino acids, that serve as the building blocks of basic cellular processes. "These are the molecules that are actually being transformed during cellular activity, and tracking them provides more direct information on what's happening at a biochemical level," Patti said.

"The idea was to apply metabolomic analysis to understand the biochemical basis of the neuropathic pain condition and reveal potential therapeutic targets," said Doctor Gary Siuzdak of the Scripps Research Centre for Metabolomics. "We call this approach 'therapeutic metabolomics'."

The scientists began with a standard model of neuropathic pain in lab rats. Patti, Siuzdak, and their colleagues sampled segments of a previously injured tibial leg nerve triggering neuropathic pain, as well as the rats' blood plasma and tissue from the rats' spinal cords. The scientists then determined the levels of metabolites in these tissues, and compared them to levels from control animals.

Unexpectedly, the scientists found that nearly all the major abnormalities in metabolite levels were present not in the injured leg nerve fibre, nor in blood plasma, but in tissue from the "dorsal horn" region of the spinal cord which normally receives signals from the tibial nerve and relays them to the brain. "After the nerve is damaged, it degrades and rebuilds itself at the site of the injury, but remodeling also occurs, possibly over a longer period, at the terminus of the nerve where it connects to dorsal horn neurons," Patti said.